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BACKGROUND: Due to widespread use of low-dose computed tomography (LDCT) screening, increasing number of patients are found to have subsolid nodules (SSNs). The management of SSNs is a clinical challenge and primarily depends on CT imaging. We seek to identify risk factors that may help clinicians determine an optimal course of management. METHODS: We retrospectively reviewed the characteristics of 83 SSN lesions, including 48 pure ground-glass nodules and 35 part-solid nodules, collected from 83 patients who underwent surgical resection. RESULTS: Of the 83 SSNs, 16 (19.28%) were benign and 67 (80.72%) were malignant, including 23 adenocarcinomas in situ (AIS), 16 minimally invasive adenocarcinomas (MIA), and 28 invasive adenocarcinomas (IA). Malignant lesions were found to have significantly larger diameters (P<0.05) with an optimal cut-off point of 9.24 mm. Significant indicators of malignancy include female sex (P<0.05), air bronchograms (P<0.001), spiculation (P<0.05), pleural tail sign (P<0.05), and lobulation (P<0.05). When compared with AIS/MIA combined, IA lesions were found to be larger (P<0.05) with an optimal cut-off of 12 mm, and have a higher percentage of part-solid nodules (P<0.001), pleural tail sign (P<0.001), air bronchograms (P<0.05), and lobulation (P<0.05). Further multivariate analysis found that lesion size and spiculation were independent factors for malignancy while part-solid nodules were associated with IA histology. CONCLUSIONS: East Asian females are at risk of presenting with a malignant lesion even without history of heavy smoking or old age. Nodule features associated with malignancy include larger size, air bronchograms, lobulation, pleural tail sign, spiculation, and solid components. A combination of patient characteristic and LDCT features can be effectively used to guide management of patients with SSNs.
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CONTEXT: Taiwanofungus camphoratus is a parasitic mushroom found in the heartwood of Cinnamomum kanehirai and is used as a nutritional supplement. It has an anticancer action, both alone and synergistically with amphotericin B (AmB). OBJECTIVE: The study intended to assess the efficacy of a T camphoratus ethanol extract (TCEE) combined with AmB for patients with metastatic cancer whose cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy. DESIGN: The research team performed a retrospective analysis as a pilot study. SETTING: The study took place at a single hospital (Taipei Medical University Hospital, Taipei, Taiwan). PARTICIPANTS: Participants were 9 patients at the hospital who were terminally ill with metastatic cancer. INTERVENTIONS: The participants had received daily doses of 2-3 g of the TCEE in combination with a weekly dose of 20-25 mg of AmB in 500 cc of 5% glucose water, given intravenously in 4-6 h. OUTCOME MEASURES: Outcome measures included (1) a primary evaluation index measuring the efficacy of the treatment; (2) a measure of tumor burden that was estimated using the response evaluation criteria in solid tumors (RECIST 1.1), (3) a secondary evaluation index measuring survival duration, and (4) safety. RESULTS: The mean treatment time was 54.4 ± 18.3 wk. At the end of the study, 2 patients showed a continued complete response, 1 patient had a continued partial response, and 1 patient showed a stable disease. The other 5 participants had times to progression ranging from 24 to 48 wk, with a mean of 35.6 wk. The mean survival time was 57.8 ± 18.5 wk, and 5 patients were still alive at the end of the study. CONCLUSIONS: For patients whose metastatic cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy, the use of TCEE as an adjuvant therapy to AmB resulted in tumor suppression and a delay in time to disease progression. The preliminary results reported here can be used to guide a future, more extensive clinical study of the combination.
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Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Antrodia/química , Produtos Biológicos/farmacologia , Metástase Neoplásica/patologia , Neoplasias/tratamento farmacológico , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Produtos Biológicos/administração & dosagem , Etanol , Humanos , Neoplasias/patologia , Projetos Piloto , Estudos Retrospectivos , Taiwan , Resultado do TratamentoRESUMO
Microfluidic-based tumor models that mimic tumor culture environment have been developed to understand the cancer metastasis mechanism and discover effective antimetastatic drugs. These models successfully recapitulated key steps of metastatic cascades, yet still limited to few metastatic steps, operation difficulty, and small molecule absorption. In this study, we developed a metastasis system made of biocompatible and drug resistance plastics to recapitulate each metastasis stage in three-dimensional (3D) mono- and co-cultures formats, enabling the investigation of the metastatic responses of cancer cells (A549-GFP). The plug-and-play feature enhances the efficiency of the experimental setup and avoids initial culture failures. The results demonstrate that cancer cells tended to proliferate and migrate with circulating flow and intravasated across the porous membrane after a period of 3 d when they were treated with transforming growth factor-beta 1 (TGF-ß1) or co-cultured with human pulmonary microvascular endothelial cells (HPMECs). The cells were also observed to detach and migrate into the circulating flow after a period of 20 d, indicating that they transformed into circulating tumor cells for the next metastasis stage. We envision this metastasis system can provide novel insights that would aid in fully understanding the entire mechanism of tumor invasion.
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Técnicas de Cocultura/instrumentação , Técnicas de Cocultura/métodos , Metástase Neoplásica/patologia , Células A549 , Movimento Celular , Endotélio Vascular/citologia , Desenho de Equipamento , Humanos , Hidrogéis , Dispositivos Lab-On-A-Chip , Células Neoplásicas Circulantes/patologia , Fator de Crescimento Transformador beta1/farmacologia , Microambiente TumoralRESUMO
The main problem in the treatment of non-small cell lung cancer (NSCLC) is metastasis. Epithelial-mesenchymal transition (EMT) is known as the critical signaling in tumor progression, metastasis, and also the drug resistance. In this study, we reported a novel gene Polymerase delta-interacting protein 2 (POLDIP2) was downregulated in NSCLC tissues and first demonstrated that overexpression of POLDIP2 increased the anchorage-independent growth (AIG) and invasiveness of H1299 cells. In addition, we examined that knockdown of POLDIP2 in H1299 and A549 cells reduced tumorigenicity and metastatic capacity in vitro and also in vivo. Moreover, downregulation of the cell proliferation marker cyclin D1 and EMT markers CDH2, Slug, and Twist was showed in H1299 cells by POLDIP2 knockdown, suggesting that the inhibition of malignancy was affected by modulating key genes for tumor growth and invasiveness. Taken together, our study is the first study that demonstrated that POLDIP2 gene was function as an oncogene in NSCLC and implied the oncogenic ability might be through promoting cell proliferation or EMT.
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Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/genética , Proteínas Nucleares/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Invasividade Neoplásica/patologia , Proteínas Nucleares/metabolismoRESUMO
PURPOSE: To assess the reduction of 6 and 12 months postoperatively of Framingham risk score in morbidly obese patients with laparoscopic sleeve gastrectomy (LSG). MATERIAL AND METHODS: In total, 870 morbid obesity patients received LSG in Taipei Medical University Hospital from June 2007 to June 2014 were retrospectively studied preoperatively, 6 and 12 months after surgery. The coronary heart disease risk was calculated using Framingham risk score. RESULTS: The body mass index in men and women decreased from 43.3 ± 6.9, 39.2 ± 6.0 kg/m2 preoperatively to 32.9 ± 6.7, 31.0 ± 5.2 kg/m2 and to 30.4 ± 5.6 , 28.2 ± 4.7 kg/m2, respectively, at 6 and 12 months after surgery (P < 0.0001). At 6 and 12 months after LSG, there was a marked improvement on lipid profile as well as a significant decline in the prevalence of diabetes mellitus, systemic hypertension, and smoking. The Framingham risk score in men and women reduced from 3.2 ± 5.7, 6.1 ± 5.7 preoperatively to 1.4 ± 5.9, 3.3 ± 5.9 and 0.1 ± 6.2, 2.8 ± 6.1, respectively, at 6 and 12 months after surgery (P < 0.0001). CONCLUSIONS: Laparoscopic sleeve gastrectomy is efficient not only in the reduction of obesity and its related comorbidities but also in decreasing the long-term coronary event risk. Early intervention for the high-risk group is strongly recommended.
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Doença das Coronárias/epidemiologia , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Adulto , Índice de Massa Corporal , Comorbidade , Doença das Coronárias/etiologia , Feminino , Seguimentos , Gastrectomia/métodos , Humanos , Laparoscopia , Lipídeos/sangue , Masculino , Obesidade Mórbida/complicações , Prevalência , Estudos Retrospectivos , Medição de Risco , Fumar/epidemiologia , Taiwan/epidemiologia , Resultado do Tratamento , Redução de PesoRESUMO
Current chemotherapeutic regimens for nonsmall cell lung cancer (NSCLC) have reached a plateau over the last few years. Targeted therapy makes use of tyrosine kinase inhibitors (TKIs) to suppress a number of signaling pathways including epidermal growth factor receptor and vascular endothelial growth factor which are active in NSCLC biology. In this study, we used sunitinib, a multi-target receptor TKI, combined with chemotherapy for unresectable/metastatic NSCLC.This open label Simon's 2 stage clinical trial enrolled a total of 6 NSCLC patients who received docetaxel (40âmg) and cisplatin (50âmg) on day 1 of each cycle (14 day interval between cycles) and sunitinib (25âmg qd for 10 days between cycles) for a total of 12 cycles (24 weeks), after which patients received maintenance therapy with vinorelbine (30âmg TIW) until disease progression. The sample size was based on a Simon's Optimal Two-Stage Designs for Phase II clinical trials. The expected response rate was set as 35% for P0 and as 60% for P1. The study was designed for a minimum of 6 patients for first stage and 15 patients until second stage with a significance level alpha = 0.10 and power = 70%. Diagnosis of a poor response in the second of 6 patients in Stage I or seventh of the 15 patients in Stage II would lead to early termination of the trial.The overall response rate was 66.7%. Four patients had an overall survival >60 months. The time to PFS ranged from 3 to 42 months. The combination therapy was well-tolerated.Sunitinib combined with chemotherapy shows promise and warrants further investigation.
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Carcinoma Pulmonar de Células não Pequenas , Cisplatino , Indóis , Neoplasias Pulmonares , Pirróis , Taxoides , Vimblastina/análogos & derivados , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Terapia de Salvação/métodos , Sunitinibe , Análise de Sobrevida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , VinorelbinaRESUMO
Cysts and cavities are common radiologic abnormalities. Pulmonary metastasis comprises a rare entity of thoracic cystic diseases. We reported a case of giant cyst at the left anterior mediastinum that was pathologically confirmed as a lung metastasis from previously resected gastric cancer. The cyst was completely removed with wedge resection of the surrounding lung through a left anterior thoracotomy. One should always keep in mind the possibility of an intrathoracic cyst near or at the mediastinal region that may originate from metastatic lesions to the lungs when patients have previous cancer history.
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Adenocarcinoma/secundário , Neoplasias Pulmonares/secundário , Cisto Mediastínico/diagnóstico , Neoplasias Gástricas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Idoso , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Seguimentos , Gastrectomia , Humanos , Biópsia Guiada por Imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Masculino , Pneumonectomia , Radiografia Torácica , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
The incidence of a fractured humeral head penetrating into the thoracic cavity is extremely rare. A 46-year-old woman presented with moderate respiratory distress at the emergency department after being involved in a motor vehicle accident. Radiographic examinations revealed fractures of the second to fifth ribs on the left side along with hemopneumothorax and fracture-dislocation of the humeral head into the thoracic cavity. After initial stabilization, video-assisted thoracic surgery (VATS) was performed to remove the fractured humeral head, and this was followed by a hemiarthroplasty. In this case report, we have discussed significant aspects of this uncommon finding in order to alert surgeons of the potential risks associated with intrathoracic displacement of the fractured humeral bone in trauma patients.
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Acidentes de Trânsito , Hemiartroplastia , Fraturas do Úmero/cirurgia , Cabeça do Úmero/lesões , Cabeça do Úmero/cirurgia , Luxação do Ombro/cirurgia , Cirurgia Torácica Vídeoassistida , Ferimentos não Penetrantes/cirurgia , Feminino , Humanos , Fraturas do Úmero/diagnóstico , Fraturas do Úmero/etiologia , Cabeça do Úmero/diagnóstico por imagem , Pessoa de Meia-Idade , Fraturas das Costelas/diagnóstico , Fraturas das Costelas/cirurgia , Luxação do Ombro/diagnóstico , Luxação do Ombro/etiologia , Traumatismos Torácicos/etiologia , Traumatismos Torácicos/cirurgia , Parede Torácica/lesões , Parede Torácica/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/etiologiaRESUMO
The radiologic appearance of multiple discrete pulmonary nodules in immunocompetent patients, with cryptococcal infection, has been rarely described. We describe a case of pulmonary cryptococcosis, presenting with bilaterally and randomly distributed nodules on a computed tomography, mimicking hematogeneous metastases. Positron emission tomography does not demonstrate 18F-fluorodeoxyglucose (FDG) uptake, suggesting a low probability for malignancy, which is a crucial piece of information for clinicians when making a management decision. We find the absence of FDG uptake correlates with the pathologic finding of an infectious nodule, composed of fibrosis and necrosis.
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Criptococose/diagnóstico por imagem , Fluordesoxiglucose F18 , Pneumopatias Fúngicas/diagnóstico por imagem , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos , Criptococose/metabolismo , Fluordesoxiglucose F18/farmacocinética , Humanos , Imunocompetência , Pneumopatias Fúngicas/metabolismo , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinéticaRESUMO
Management of empyema with bronchopleural fistula remains a challenge. A 38-year-old man who had bullous emphysema was hospitalized on account of a right-sided necrotizing pneumonia complicated by empyema that mandated a tube drainage. Persistent air leak from the chest tube was noted, and chest computed tomography confirmed an empyema cavity with a suspicious bronchopleural fistula. This complex condition was successfully treated using fibrin glue with buttressed bovine pericardium to seal the fistula, followed by obliteration of the empyema cavity using a pedicled muscle flap of the latissimus dorsi. There was no recurrence of empyema at a follow-up 5 years after this procedure.
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Fístula Brônquica/cirurgia , Empiema/cirurgia , Pericárdio/transplante , Doenças Pleurais/cirurgia , Fístula do Sistema Respiratório/cirurgia , Retalhos Cirúrgicos , Adulto , Animais , Bovinos , Humanos , Masculino , Transplante HeterólogoRESUMO
OBJECTIVES: The aim of this study was to evaluate whether chest radiographs could offer useful information for the assessment of pectus excavatum (PE) before and after Nuss repair in adults. METHODS: A total of 154 adults, with a mean age of 24.0 ± 5.0 years (range, 18-44 years), who underwent a Nuss repair of PE, with a mean follow-up of 42 months (range, 14-71 months), were included in this retrospective study. Sixty-two of these patients were also evaluated after the pectus bar removal, with a mean follow-up of 13 months (range, 6-44 months). The preoperative and postoperative imaging modalities were compared. RESULTS: The preoperative mean Haller indices measured on computed tomography (CT) and chest radiographs were 4.61 ± 1.58 (range, 2.6-11.9) and 3.82 ± 1.17 (range, 2.0-10.2), respectively. The Pearson correlation coefficient between the two parameters was 0.757. The postoperative mean Haller index measured on chest radiographs was 2.86 ± 0.56 (range, 1.7-5.4) and showed statistically significant improvement compared with the preoperative index (P < 0.001). The mean sternovertebral (SV) distances detected on preoperative and postoperative (>6 months after surgery) lateral chest radiographs were 7.67 ± 1.89 cm (range, 2.5-12.9 cm) and 9.89 ± 1.80 cm (range, 4.6-15.0 cm), respectively, showing statistically significant improvement (P < 0.001). The mean sternovertebral (SV) distance in patients after the bar removal detected on lateral chest radiographs was 9.25 ± 2.14 cm, also showing statistically significant improvement compared with the preoperative value (P < 0.001). CONCLUSIONS: Haller indices measured using chest radiographs and CT showed a strong correlation. Therefore, chest radiographs can be used as an alternative tool for the preoperative evaluation of PE. The Nuss operation significantly improved SV distances detected on lateral chest radiographs. Lateral chest radiographs can be used as a simple modality for the objective quantitative assessment of the anatomic results and follow-up of the Nuss operation in adults.
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Tórax em Funil/diagnóstico por imagem , Cirurgia Torácica Vídeoassistida/métodos , Adolescente , Adulto , Feminino , Tórax em Funil/cirurgia , Humanos , Masculino , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Toracoscopia/métodos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The optimal treatment strategy for patients with operable stage IIIA (N2) non-small cell lung cancer is uncertain. We performed a systematic review and meta-analysis to test the hypothesis that the addition of radiotherapy to induction chemotherapy prior to surgical resection does not improve survival compared with induction chemotherapy alone. METHODS: A comprehensive search of PubMed for relevant studies comparing patients with stage IIIA (N2) non-small cell lung cancer undergoing resection after treatment with induction chemotherapy alone or induction chemoradiotherapy was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Hazard ratios were extracted from these studies to give pooled estimates of the effect of induction therapy on overall survival. RESULTS: There were 7 studies that met criteria for analysis, including 1 randomized control trial, 1 phase II study, 3 retrospective reviews, and 2 published abstracts of randomized controlled trials. None of the studies demonstrated a survival benefit to adding induction radiation to induction chemotherapy versus induction chemotherapy alone. The meta-analysis performed on randomized studies (n=156 patients) demonstrated no benefit in survival from adding radiation (hazard ratio 0.93, 95% confidence interval 0.54 to 1.62, p=0.81), nor did the meta-analysis performed on retrospective studies (n=183 patients, hazard ratio 0.77, 95% confidence interval 0.50 to 1.19, p=0.24). CONCLUSIONS: Published evidence is sparse but does not support the use of radiation therapy in induction regimens for stage IIIA (N2). Given the potential disadvantages of adding radiation preoperatively, clinicians should consider using this treatment strategy only in the context of a clinical trial to allow better assessment of its effectiveness.
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Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Intervalo Livre de Doença , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , PneumonectomiaRESUMO
OBJECTIVES: The aim of this study was to assess the standard uptake value in clinical stage I non-small cell lung cancer (NSCLC) and its correlation with pathological status and prognosis. METHODS: We retrospectively reviewed 674 patients diagnosed with NSCLC between January 2002 and June 2005. Patients with clinical stage I diseases undergone a preoperative positron emission tomography-computed tomography scan followed by anatomic resection. We reviewed the clinical features of 152 patients with an average follow-up of 87 months. RESULTS: We analysed the clinical features of 108 patients with stage I NSCLC and 44 patients with non-stage I NSCLC. There were no statistical differences in age, histological type, location or tumour differentiation between the two groups. In the Stage I group, the patients had lower maximum standard uptake value (SUVmax; 3.80 ± 3.17 vs 5.73 ± 3.65, P = 0.001), lower carcinoembryonic antigen (CEA) levels (2.86 ± 4.80 vs 9.11 ± 17.21 ng/ml, P = 0.027) and smaller tumour size (2.39 ± 0.98 vs 3.73 ± 2.04 cm, P < 0.001). The patients with higher SUVmax had a more advanced pathological stage, poorer tumour differentiation and larger tumour size. A higher SUVmax was an independent factor predicting an advanced pathological stage (SUVmax ≥ 3.3, odds ratio 3.246). The median survival of patients with SUVmax ≥ 3.3 and SUVmax <3.3 were 64.32 and 53.08 months, respectively (P = 0.654). CONCLUSIONS: Higher preoperative 18-fluorodeoxyglucose uptake by a tumour was significantly associated with an advanced pathological stage but not correlated with a poorer prognosis. An aggressive preoperative work-up for occult N2 disease should be emphasized, avoiding inappropriate thoracotomy.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Métodos Epidemiológicos , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We studied the effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, on colon cancer. The expression of HDACs in colorectal cancer specimens and the effects of SAHA on colon cancer cells and tumors of nude mice were assessed. Treatment with SAHA (3 µm) for 72 h induced downregulation of different subtypes of HDAC proteins and also induced acetylation of histone 3 and histone 4. SAHA significantly inhibited the expression of the oncogenic protein c-myc and also increased the expression of the p53 and Rb proteins. The immunohistochemical staining of HDACs, including HDAC1, HDAC2, HDAC3, and HDAC4, was significantly increased in colorectal adenocarcinoma specimens compared to healthy control tissues. In addition, murine studies showed that 100 mg/kg SAHA administered by intraperitoneal injection significantly induced tumor necrosis and inhibited the growth of colon tumors. Immunohistochemistry of the tumor tissues from nude mice revealed that SAHA inhibited the expression of different subtypes of histone deacetylase, the anti-apoptotic proteins cyclin D1, survivin, and also inhibited cell proliferative as determined by Ki67 expression. SAHA inhibited the growth of colon tumors by decreasing histone deacetylases and the expression of cyclin D1 and survivin in nude mice.
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Neoplasias Colorretais/metabolismo , Ciclina D1/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/química , Histona Desacetilases/metabolismo , Ácidos Hidroxâmicos/farmacologia , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas Repressoras/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Western Blotting , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Survivina , Análise Serial de Tecidos , Células Tumorais Cultivadas , VorinostatRESUMO
BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) signaling reportedly promotes tumor malignancy and recurrence in nonsmall cell lung cancer (NSCLC). It was demonstrated previously that the STAT3 pathway maintains the tumorigenicity and therapeutic resistance of malignant tumors as well as cancer stem cells (CSCs). The objective of the current study was to investigate the effect of the strong STAT3 inhibitor, cucurbitacin I, in prominin-1 (CD133)-positive lung cancer cells. METHODS: CD133-positive and CD133-negative NSCLC-derived cells were isolated from 7 patients with NSCLC. CD133-positive NSCLC cells that were treated with or without cucurbitacin I were evaluated for their expression of phosphorylated STAT3 (p-STAT3), tumorigenicity, stemness properties, and resistance to chemotherapeutic drugs and ionizing radiation. RESULTS: Compared with parental or CD133-negative NSCLC cells, CD133-positive NSCLC cells had greater tumorigenicity, greater radioresistance, and higher expression of octamer-binding transcription factor 4 (Oct-4), Nanog homeobox, and sex-determining region Y, box 2 (Sox2) at high p-STAT3 levels. Cucurbitacin I treatment at 100 nM effectively abrogated STAT3 activation, tumorigenic capacity, sphere formation ability, radioresistance, and chemoresistance in CD133-positive NSCLC cells. Microarray data suggested that cucurbitacin I inhibited the stemness gene signature of CD133-positive NSCLC cells and facilitated the differentiation of CD133-positive NSCLC cells into CD133-negative NSCLC cells. It is noteworthy that 150 nM cucurbitacin I effectively blocked STAT3 signaling and downstream survival targets, such as B-cell chronic lymphocytic leukemia/lymphoma 2 (Bcl-2) and Bcl-2-like 1 (Bcl-xL) expression and induced apoptosis in CD133-positive NSCLC cells. Finally, xenotransplantation experiments revealed that cucurbitacin I plus radiotherapy or chemotherapeutic drugs significantly suppressed tumorigenesis and improved survival in NSCLC-CD133-positive-transplanted, immunocompromised mice. CONCLUSIONS: Targeting STAT3 signaling in CD133-positive NSCLC cells with cucurbitacin I suppressed CSC-like properties and enhanced chemoradiotherapy response. The potential of cucurbitacin I should be verified further in future anti-CSC therapy.
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Antígenos CD/análise , Carcinoma Pulmonar de Células não Pequenas , Glicoproteínas/análise , Neoplasias Pulmonares , Células-Tronco Neoplásicas/efeitos dos fármacos , Peptídeos/análise , Fator de Transcrição STAT3/antagonistas & inibidores , Triterpenos/farmacologia , Antígeno AC133 , Idoso , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Proliferação de Células , Separação Celular , Resistencia a Medicamentos Antineoplásicos , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Camundongos , Pessoa de Meia-Idade , Proteína Homeobox Nanog , Metástase Neoplásica , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação , Fator 3 de Transcrição de Octâmero/biossíntese , Fator 3 de Transcrição de Octâmero/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Tolerância a Radiação , Fatores de Transcrição SOXB1/biossíntese , Fatores de Transcrição SOXB1/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Proteína bcl-X/genéticaRESUMO
BACKGROUND: Histone deacetylases and histone acetyl transferases covalently modify histone proteins, consequentially altering chromatin architecture and gene expression. METHODS: The effects of suberoylanilide hydroxamic acid, a HDAC inhibitor, on 320 HSR colon cells were assessed in 320 HSR colon cancer cells. RESULTS: Concentration and time-dependent inhibition of 320 HSR cell proliferation was observed. Treatment of 320 HSR cells with 5 µM SAHA for 72 h significantly inhibited their growth by 50% as compared to that of the control. Fluorescence-activated cell sorting analysis demonstrated significant inhibition of cell cycle progression (sub-G1 arrest) and induction of apoptosis upon various SAHA concentrations after 48 h. In addition, the anti-apoptosis proteins, survivin and Bcl-xL, were significantly inhibited by SAHA after 72 h of treatment. Immunocytochemistry analysis revealed that SAHA-resistant cells were positive for cyclin A (85%), ki-67 (100%), p53 (100%), survivin (100%), and p21 (90%) expression. Furthermore, a significant increase cyclin A-, Ki-67-, p53-, survivin-, and p21-positive cells were noted in SAHA-resistant tumor cells. CONCLUSION: Our results demonstrated for the first time in 320 HSR colon adenocarcinoma cells that SAHA might be considered as an adjuvant therapy for colon adenocarcinoma.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Fase G1/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/fisiologia , Proliferação de Células/efeitos dos fármacos , Separação Celular , Quimioterapia Adjuvante , Citometria de Fluxo , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , VorinostatRESUMO
BACKGROUND AND OBJECTIVE: Primary spontaneous pneumothorax (PSP) is a common condition that typically affects young adults. With recent advances in techniques, VATS is now a safe and accepted procedure for treating PSP. Lung isolation techniques have been commonly used to facilitate surgical procedures in the past. The purpose of this study was to evaluate the feasibility of using a single-lumen endotracheal tube for thoracoscopic surgery in patients with PSP. METHODS: A series of 121 consecutive patients with PSP, who underwent VATS using a double-lumen or single-lumen endotracheal tube between January 2000 and December 2002, were assessed retrospectively. The clinical features, operation times, complications, hospital stays and recurrences of PSP in these patients were recorded and analysed. RESULTS: There were no significant differences in gender, BMI, smoking habits, blebs/bullae on CT, duration of surgery or recurrence of PSP between the two groups. Patients in the single-lumen endotracheal tube group had a shorter duration of anaesthesia (15.4 +/- 2.6 vs 25.6 +/- 3.2 min, P < 0.001), lower early complication rates, lower costs and shorter hospital stays (3.6 +/- 3.0 vs 4.5 +/- 2.8 days, P = 0.02) compared with those in the double-lumen endotracheal tube group. The follow-up period was 40-68 months (mean 54 months). There were two recurrences in each group (3.1% vs 3.4%). CONCLUSIONS: VATS for the treatment of PSP was easily performed using a single-lumen endotracheal tube, and resulted in lower intubation-related costs, fewer complications and equivalent outcomes, compared with procedures performed using double-lumen endotracheal tube anaesthesia.
Assuntos
Anestesia Endotraqueal , Anestésicos/administração & dosagem , Intubação Intratraqueal/efeitos adversos , Pneumotórax/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Intubação Intratraqueal/economia , Tempo de Internação , Pulmão/cirurgia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The urinary proteome is known to be a valuable field of study related to human physiological functions because many components in urine provide an alternative to blood plasma as a potential source of disease biomarkers useful in clinical diagnosis and therapeutic application. Due to the variability and complexity of urine, sample preparation is very important for decreasing the dynamic range of components and isolating specific urinary proteins prior to analysis. We discuss many useful sample preparation methods in this chapter, including those of lung cancer urine samples. In addition, protein detection methods are also crucial in visualizing protein profiles and for quantification of protein content in urine samples from both normal donor and lung cancer patients. This chapter also provides alternative choices of urine sample preparation and detection methods for selective use in urinary proteome analysis and for identifying urinary protein markers in lung cancer and other diseases.